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Inhibitor of Apoptosis Proteins and Caspases

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Apoptosis, Cell Signaling, and Human Diseases

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Summary

Inhibitors of apoptosis proteins (IAPs) were first identified as insect viral proteins that block host cell apoptosis. Cellular homologs bearing the characteristic baculoviral IAP repeat (BIR) domain have now been found in all metazoans and have more diverse functions than their name suggests. Some cellular IAPs do, in fact, inhibit apoptosis, in part at least by directly inhibiting cysteine proteases, called caspases, that are ultimately responsible for killing a cell. The primary aim of this chapter is to explore the intricate regulation of caspases by IAPs, and the exquisite counter regulation of IAPs by antagonist proteins. Interest in IAPs extends beyond apoptosis pathways and recent evidence suggests that IAPs modulate cell-signaling pathways that affect growth and proliferation and some of these remarkable studies will be discussed.

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References

  1. Clem RJ, Fechheimer M, Miller LK. Prevention of apoptosis by a baculovirus gene during infection of insect cells. Science 1991;254:1388–1390

    PubMed  CAS  Google Scholar 

  2. Crook NE, Clem RJ, Miller LK. An apoptosis inhibiting baculovirus gene with a zinc finger like motif. J Virol 1993;67:2168–2174.

    PubMed  CAS  Google Scholar 

  3. Birnbaum MJ, Clem RJ, Miller LK. An apoptosis inhibiting gene from a nuclear polyhedrosis virus encoding a polypeptide with cys/his sequence motif. J Virol 1994;68:2521–2528.

    PubMed  CAS  Google Scholar 

  4. Hawkins CJ, Uren AG, Hacker G, Medcalf RL, Vaux DL. Inhibition of interleukin 1-betaconverting enzyme-mediated apoptosis of mammalian cells by baculovirus IAP. Proc Natl Acad Sci USA 1996;93:13,786–13,790.

    PubMed  CAS  Google Scholar 

  5. Hay BA, Wassarman DA, Rubin GM. Drosophila homologs of baculovirus inhibitor of apoptosis proteins function to block cell death. Cell 1995;83:1253–1262.

    PubMed  CAS  Google Scholar 

  6. Liston P, Roy N, Tamai K, et al. Suppression of apoptosis in mammalian cells by NAIP and a related family of IAP genes. Nature 1996;379:349–353.

    PubMed  CAS  Google Scholar 

  7. Duckett CS, Nava VE, Gedrich RW, et al. A conserved family of cellular genes related to the baculovirus IAP gene and encoding apoptosis inhibitors. EMBO J 1996;15:2685–2694.

    PubMed  CAS  Google Scholar 

  8. Uren AG, Pakusch M, Hawkins CJ, Puls KL, Vaux DL. Cloning and expression of apoptosis inhibitory protein homologs that function to inhibit apoptosis and/or bind tumor necrosis factor receptor-associated factors. Proc Natl Acad Sci USA 1996;93:4974–4978.

    PubMed  CAS  Google Scholar 

  9. Rothe M, Pan MG, Henzel WJ, Ayres TM, Goeddel DV. The TNFR2-TRAF signaling complex contains two novel proteins related to baculoviral-inhibitor of apoptosis proteins. Cell 1995;83:1243–1252.

    PubMed  CAS  Google Scholar 

  10. Deveraux QL, Takahashi R, Salvesen GS, Reed JC. X-linked IAP is a direct inhibitor of cell-death proteases. Nature 1997;388:300–304.

    PubMed  CAS  Google Scholar 

  11. Deveraux QL, Roy N, Stennicke HR, et al. IAPs block apoptotic events induced by caspase-8 and cytochrome c by direct inhibition of distinct caspases. EMBO J 1998;17:2215–2223.

    PubMed  CAS  Google Scholar 

  12. Roy N, Deveraux QL, Takahashi R, Salvesen GS, Reed JC. The c-IAP-1 and c-IAP-2 proteins are direct inhibitors of specific caspases. EMBO J 1997;16:6914–6925.

    PubMed  CAS  Google Scholar 

  13. Riedl SJ, Fuentes-Prior P, Renatus M, et al. Structural basis for the activation of human procaspase-7. Proc Natl Acad Sci USA 2001;98:14,790–14,795.

    PubMed  CAS  Google Scholar 

  14. Riedl SJ, Renatus M, Schwarzenbacher R, et al. Structural basis for the inhibition of caspase-3 by XIAP. Cell 2001;104:791–800.

    PubMed  CAS  Google Scholar 

  15. Shiozaki EN, Chai J, Rigotti DJ, et al. Mechanism of XIAP-mediated inhibition of caspase-9. Mol Cell 2003;11:519–527.

    PubMed  CAS  Google Scholar 

  16. Scott FL, Denault JB, Riedl SJ, Shin H, Renatus M, Salvesen GS. XIAP inhibits caspase-3 and-7 using two binding sites: Evolutionarily conserved mechanism of IAPs. Embo J 2005;24:645–655.

    PubMed  CAS  Google Scholar 

  17. Huang Y, Park YC, Rich RL, Segal D, Myszka DG, Wu H. Structural basis of caspase inhibition by XIAP: Differential roles of the linker versus the BIR domain. Cell 2001;104:781–790.

    PubMed  CAS  Google Scholar 

  18. Uren AG, Coulson EJ, Vaux DL. Conservation of baculovirus inhibitor of apoptosis repeat proteins (BIRPs) in viruses, nematodes, vertebrates and yeasts. Trends Biochem Sci 1998;23:159–162.

    PubMed  CAS  Google Scholar 

  19. Hinds MG, Norton RS, Vaux DL, Day CL. Solution structure of a baculoviral inhibitor of apoptosis (IAP) repeat. Nat Struct Biol 1999;6:648–651.

    PubMed  CAS  Google Scholar 

  20. Sun C, Cai M, Meadows RP, et al. NMR structure and mutagenesis of the third BIR domain of the inhibitor of apoptosis protein XIAP. J Biol Chem 2000;275:33,777–33,781.

    PubMed  CAS  Google Scholar 

  21. Sun C, Cai M, Gunasekera AH, et al. NMR structure and mutagenesis of the inhibitor-ofapoptosis protein XIAP. Nature 1999;401:818–822.

    PubMed  CAS  Google Scholar 

  22. Barlow PN, Luisi B, Milner A, Elliott M, Everett R. Structure of the C3HC4 domain by 1hnuclear magnetic resonance spectroscopy. A new structural class of zinc-finger. J Mol Biol 1994;237:201–211.

    PubMed  CAS  Google Scholar 

  23. Borden KL, Boddy MN, Lally J, et al. The solution structure of the ring finger domain from the acute promyelocytic leukaemia proto-oncoprotein PML. EMBO J 1995;14:1532–1541.

    PubMed  CAS  Google Scholar 

  24. Yang Y, Fang SY, Jensen JP, Weissman AM, Ashwell JD. Ubiquitin protein ligase activity of IAPs and their degradation in proteasomes in response to apoptotic stimuli. Science 2000;288:874–877.

    PubMed  CAS  Google Scholar 

  25. Tschopp J, Martinon F, Burns K. Nalps: A novel protein family involved in inflammation. Nat Rev Mol Cell Biol 2003;4:95–104.

    PubMed  CAS  Google Scholar 

  26. Hauser HP, Bardroff M, Pyrowolakis G, Jentsch S. A giant ubiquitin-conjugating enzyme related to IAP apoptosis inhibitors. J Cell Biol 1998;141:1415–1422.

    PubMed  CAS  Google Scholar 

  27. Hawkins CJ, Yoo SJ, Peterson EP, Wang SL, Vernooy SY, Hay BA. The drosophila caspase Dronc cleaves following glutamate or aspartate and is regulated by DIAP1, HID, and GRIM. J Biol Chem 2000;275:27,084–27,093.

    PubMed  CAS  Google Scholar 

  28. Nicholson DW. Caspase structure, proteolytic substrates, and function during apoptotic cell death. Cell Death Differ 1999;6:1028–1042.

    PubMed  CAS  Google Scholar 

  29. Thornberry NA, Ranon TA, Pieterson EP, et al. A combinatorial approach defines specificities of members of the caspase family and granzyme B-functional, relationships established for key mediators of apoptosis. J Biol Chem 1997;272:17,907–17,911.

    PubMed  CAS  Google Scholar 

  30. Stennicke HR, Deveraux QL, Humke EW, Reed JC, Dixit VM, Salvesen GS. Caspase-9 can be activated without proteolytic processing. J Biol Chem 1999;274:8359–8362.

    PubMed  CAS  Google Scholar 

  31. Boatright KM, Renatus M, Scott FL, et al. A unified model for apical caspase activation. Mol Cell 2003;11:529–541.

    PubMed  CAS  Google Scholar 

  32. Silke J, Ekert PG, Day CL, et al. Direct inhibition of caspase 3 is dispensable for the antiapoptotic activity of XIAP. EMBO J 2001;20:3114–3123.

    PubMed  CAS  Google Scholar 

  33. Takahashi R, Deveraux Q, Tamm I, et al. A single BIR domain of XIAP sufficient for inhibiting caspases. J Biol Chem 1998;273:7787–7790.

    PubMed  CAS  Google Scholar 

  34. Silke J, Hawkins CJ, Ekert PG, et al. The anti-apoptotic activity of XIAP is retained upon mutation of both the caspase 3-and caspase 9-interacting sites. J Cell Biol 2002;157:115–124.

    PubMed  CAS  Google Scholar 

  35. Chai J, Shiozaki E, Srinivasula SM, et al. Structural basis of caspase-7 inhibition by XIAP. Cell 2001;104:769–780.

    PubMed  CAS  Google Scholar 

  36. Yan N, Wu JW, Chai J, Li W, Shi Y. Molecular mechanisms of Drice inhibition by DIAP1 and removal of inhibition by REAPER, HID and GRIM. Nat Struct Mol Biol 2004;11:420–428.

    PubMed  CAS  Google Scholar 

  37. Deveraux QL, Leo E, Stennicke HR, Welsh K, Salvesen GS, Reed JC. Cleavage of human inhibitor of apoptosis protein XIAP results in fragments with distinct specificities for caspases. EMBO J 1999;18:5242–5251.

    PubMed  CAS  Google Scholar 

  38. Srinivasula SM, Hegde R, Saleh A, et al. A conserved XIAP-interaction motif in caspase-9 and Smac/DIABLO regulates caspase activity and apoptosis. Nature 2001;410:112–116.

    PubMed  CAS  Google Scholar 

  39. Wu G, Chai J, Suber TL, et al. Structural basis of IAP recognition by Smac/DIABLO. Nature 2000;408:1008–1012.

    PubMed  CAS  Google Scholar 

  40. Renatus M, Stennicke HR, Scott FL, Liddington RC, Salvesen GS. Dimer formation drives the activation of the cell death protease caspase-9. Proc Natl Acad Sci USA 2001;98: 14,250–14,255.

    PubMed  CAS  Google Scholar 

  41. Suzuki Y, Nakabayashi Y, Nakata K, Reed JC, Takahashi R. X-linked inhibitor of apoptosis protein (XIAP) inhibits caspase-3 and-7 in distinct modes. J Biol Chem 2001;276: 27,058–27,063.

    PubMed  CAS  Google Scholar 

  42. Tenev T, Zachariou A, Wilson R, Ditzel M, Meier P. IAPs are functionally non-equivalent and regulate effector caspases through distinct mechanisms. Nat Cell Biol 2005;7:70–77.

    PubMed  CAS  Google Scholar 

  43. Ho PK, Jabbour AM, Ekert PG, Hawkins CJ. Caspase-2 is resistant to inhibition by inhibitor of apoptosis proteins (IAPs) and can activate caspase-7. FEBS J 2005;272:1401–1414.

    PubMed  CAS  Google Scholar 

  44. Woo M, Hakem R, Soengas MS, et al. Essential contribution of caspase 3 CPP32 to apoptosis and its associated nuclear changes. Genes Dev 1998;12:806–819.

    PubMed  CAS  Google Scholar 

  45. Hakem R, Hakem A, Duncan GS, et al. Differential requirement for caspase 9 in apoptotic pathways in vivo. Cell 1998;94:339–352.

    PubMed  CAS  Google Scholar 

  46. Kuida K, Haydar TF, Kuan CY, et al. Reduced apoptosis and cytochrome c-mediated caspase activation in mice lacking caspase-9. Cell1998;94:325–337.

    PubMed  CAS  Google Scholar 

  47. Yoshida H, Kong YY, Yoshida R, et al. Apaf1 is required for mitochondrial pathways of apoptosis and brain development. Cell 1998;94:739–750.

    PubMed  CAS  Google Scholar 

  48. Vucic D, Stennicke HR, Pisabarro MT, Salvesen GS, Dixit VM. ML-IAP, a novel inhibitor of apoptosis that is preferentially expressed in human melanomas. Curr Biol 2000;10:1359–1366.

    PubMed  CAS  Google Scholar 

  49. Kasof GM, Gomes BC. Livin, a novel inhibitor of apoptosis protein family member. J Biol Chem 2001;276:3238–3246.

    PubMed  CAS  Google Scholar 

  50. Lin JH, Deng G, Huang Q, Morser J. Kiap, a novel member of the inhibitor of apoptosis protein family. Biochem Biophys Res Commun 2000;279:820–831.

    PubMed  CAS  Google Scholar 

  51. Vucic D, Franklin MC, Wallweber HJ, et al. Engineering ML-IAP to produce an extraordinarily potent caspase-9 inhibitor: Implications for Smac-dependent anti-apoptotic activity of ML-IAP. Biochem J 2005;385:11–20.

    PubMed  CAS  Google Scholar 

  52. Roy N, Mahadevan MS, Mclean M, et al. The gene for neuronal apoptosis inhibitory protein is partially deleted in individuals with spinal muscular atrophy. Cell 1995;80:167–178.

    PubMed  CAS  Google Scholar 

  53. Chang JG, Jong YJ, Lin SP, et al. Molecular analysis of survival motor neuron (SMA) and neuronal apoptosis inhibitory protein (NAIP) genes of spinal muscular atrophy patients and their parents. Hum Genet 1997;100:577–581.

    PubMed  CAS  Google Scholar 

  54. Campbell L, Potter A, Ignatius J, Dubowitz V, Davies K. Genomic variation and gene conversion in spinal muscular atrophy-implications for disease process and clinical phenotype. Am J Hum Genet 1997;61:40–50.

    PubMed  CAS  Google Scholar 

  55. Harton JA, Linhoff MW, Zhang J, Ting JP. Cutting edge: Caterpiller: A large family of mammalian genes containing card, pyrin, nucleotide-binding, and leucine-rich repeat domains. J Immunol 2002;169:4088–4093.

    PubMed  CAS  Google Scholar 

  56. Maier JK, Lahoua Z, Gendron NH, et al. The neuronal apoptosis inhibitory protein is a direct inhibitor of caspases-3 and-7. J Neurosci 2002;22:2035–2043.

    PubMed  CAS  Google Scholar 

  57. Wright EK, Goodart SA, Growney JD, et al. NAIP5 affects host susceptibility to the intracellular pathogen legionella pneumophila. Curr Biol 2003;13:27–36.

    PubMed  CAS  Google Scholar 

  58. Diez E, Lee SH, Gauthier S, et al. BIRc1e is the gene within the lgn1 locus associated with resistance to legionella pneumophila. Nat Genet 2003;33:55–60.

    PubMed  CAS  Google Scholar 

  59. Hauser HP, Bardroff M, Pyrowolakis G, Jentsch S. A giant ubiquitin-conjugating enzyme related to IAP apoptosis inhibitors. J Cell Biol 1998;141:1415–1422.

    PubMed  CAS  Google Scholar 

  60. Chen Z, Naito M, Hori S, Mashima T, Yamori T, Tsuruo T. A human IAP-family gene, apollon, expressed in human brain cancer cells. Biochem Biophys Res Commun 1999;264:847–854.

    PubMed  CAS  Google Scholar 

  61. Bartke T, Pohl C, Pyrowolakis G, Jentsch S. Dual role of Bruce as an antiapoptotic IAP and a chimeric E2/E3 ubiquitin ligase. Mol Cell 2004;14:801–811.

    PubMed  CAS  Google Scholar 

  62. Ambrosini G, Adida C, Altieri DC. A novel anti-apoptosis gene, Survivin, expressed in cancer and lymphoma. Nat Med 1997;3:917–921.

    PubMed  CAS  Google Scholar 

  63. Muchmore SW, Chen J, Jakob C, et al. Crystal structure and mutagenic analysis of the inhibitor-of-apoptosis protein Survivin. Mol Cell 2000;6:173–182.

    PubMed  CAS  Google Scholar 

  64. Verdecia MA, Huang H, Dutil E, Kaiser DA, Hunter T, Noel JP. Structure of the human antiapoptotic protein Survivin reveals a dimeric arrangement. Nat Struct Biol 2000;7:602–608.

    PubMed  CAS  Google Scholar 

  65. Tamm I, Wang Y, Sausville E, et al. Iap-family protein survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs. Cancer Res 1998;58:5315–5320.

    PubMed  CAS  Google Scholar 

  66. Shin S, Sung BJ, Cho YS, et al. An anti-apoptotic protein human Survivin is a direct inhibitor of caspase-3 and-7. Biochemistry 2001;40:1117–1123.

    PubMed  CAS  Google Scholar 

  67. Conway EM, Pollefeyt S, Cornelissen J, et al. Three differentially expressed Survivin cDNA variants encode proteins with distinct antiapoptotic functions. Blood 2000;95:1435–1442.

    PubMed  CAS  Google Scholar 

  68. Banks DP, Plescia J, Altieri DC, et al. Survivin does not inhibit caspase-3 activity. Blood 2000;96:4002–4003.

    PubMed  CAS  Google Scholar 

  69. White K, Grether ME, Abrams JM, Young L, Farrell K, Steller H. Genetic control of programmed cell death in drosophila. Science 1994;264:677–683.

    PubMed  CAS  Google Scholar 

  70. Grether ME, Abrams JM, Agapite J, White K, Steller H. The head involution defective gene of drosophila melanogaster functions in programmed cell death. Genes Dev 1995;9: 1694–1708.

    PubMed  CAS  Google Scholar 

  71. Chen P, Nordstrom W, Gish B, Abrams JM. Grim, a novel cell death gene in drosophila. Genes Dev 1996;10:1773–1782.

    PubMed  CAS  Google Scholar 

  72. Srinivasula SM, Datta P, Kobayashi M, et al. Sickle, a novel drosophila death gene in the reaper/hid/grim region, encodes an IAP-inhibitory protein. Curr Biol 2002;12:125–130.

    PubMed  CAS  Google Scholar 

  73. Claveria C, Caminero E, Martinez-A C, Campuzano S, Torres M. GH3, a novel proapoptotic domain in drosophila GRIM, promotes a mitochondrial death pathway. EMBO J 2002;21:3327–3336.

    PubMed  CAS  Google Scholar 

  74. Zachariou A, Tenev T, Goyal L, Agapite J, Steller H, Meier P. IAP-antagonists exhibit nonredundant modes of action through differential DIAP1 binding. EMBO J 2003;22:6642–6652.

    PubMed  CAS  Google Scholar 

  75. Tenev T, Zachariou A, Wilson R, Paul A, Meier P. Jafrac2 is an IAP antagonist that promotes cell death by liberating Dronc from DIAP1. EMBO J 2002;21:5118–5129.

    PubMed  CAS  Google Scholar 

  76. Haining WN, Carboy-Newcomb C, Wei CL, Steller H. The proapoptotic function of drosophila HID is conserved in mammalian cells. Proc Natl Acad Sci USA 1999;96: 4936–4941.

    PubMed  CAS  Google Scholar 

  77. Claveria C, Albar JP, Serrano A, et al. Drosophila GRIM induces apoptosis in mammalian cells. EMBO J 1998;17:7199–7208.

    PubMed  CAS  Google Scholar 

  78. Vucic D, Kaiser WJ, Miller LK. Inhibitor of apoptosis proteins physically interact with and block apoptosis induced by drosophila proteins HID and GRIM. Mol Cell Biol 1998;18:3300–3309.

    PubMed  CAS  Google Scholar 

  79. Mccarthy JV, Dixit VM. Apoptosis induced by drosophila Reaper and Grim in a human system-attenuation by inhibitor of apoptosis proteins (cIAPs). J Biol Chem 1998;273: 24,009–24,015.

    PubMed  CAS  Google Scholar 

  80. Goyal L, McCall K, Agapite J, Hartwieg E, Steller H. Induction of apoptosis by drosophila Reaper, HID and Grim through inhibition of IAP function. EMBO J 2000;19:589–597.

    PubMed  CAS  Google Scholar 

  81. Wang SL, Hawkins CJ, Yoo SJ, Müller H-AJ, Hay BA. The drosophila caspase inhibitor DIAP1 is essential for cell survival and is negatively regulated by HID. Cell 1999;98:453–463.

    PubMed  CAS  Google Scholar 

  82. Chai J, Yan N, Huh JR, et al. Molecular mechanism of Reaper-Grim-HID-mediated suppression of DIAP1-dependent Dronc ubiquitination. Nat Struct Biol 2003;10:892–898.

    PubMed  CAS  Google Scholar 

  83. Du C, Fang M, Li Y, Li L, Wang X. Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition. Cell 2000;102:33–42.

    PubMed  CAS  Google Scholar 

  84. Verhagen A, Ekert PG, Silke J, et al. Identification of DIABLO, a mammalian protein that promotes apoptosis by binding to and antagonizing IAP proteins. Cell 2000;102:43–53.

    PubMed  CAS  Google Scholar 

  85. Hegde R, Srinivasula SM, Datta P, et al. The polypeptide chain-releasing factor GSPT1/eRF3 is proteolytically processed into an IAP-binding protein. J Biol Chem 2003; 278:38,699–38,706.

    PubMed  CAS  Google Scholar 

  86. Verhagen AM, Silke J, Ekert PG, et al. HTRA2 promotes cell death through its serine protease activity and its ability to antagonise inhibitor of apoptosis proteins. J Biol Chem 2001;277:445–454.

    PubMed  Google Scholar 

  87. Liston P, Fong WG, Kelly NL, et al. Identification of XAF1 as an antagonist of XIAP anticaspase activity. Nat Cell Biol 2001;3:128–133.

    PubMed  CAS  Google Scholar 

  88. Wilkinson JC, Richter BW, Wilkinson AS, et al. VIAF, a conserved inhibitor of apoptosis (IAP)-interacting factor that modulates caspase activation. J Biol Chem 2004;279:51,091–51,099.

    PubMed  CAS  Google Scholar 

  89. Ekert PG, Silke J, Hawkins CJ, Verhagen AM, Vaux DL. DIABLO promotes apoptosis by removing MIHA/XIAP from processed caspase 9. J Cell Biol 2001;152:483–490.

    PubMed  CAS  Google Scholar 

  90. van Loo G, van Gurp M, Depuydt B, et al. The serine protease OMI/HTRA2 is released from mitochondria during apoptosis. OMI interacts with caspase-inhibitor XIAP and induces enhanced caspase activity. Cell Death Differ 2002;9:20–26.

    PubMed  Google Scholar 

  91. Martins LM, Iaccarino I, Tenev T, et al. The serine protease OMI/HTRA2 regulates apoptosis by binding XIAP through a reaper-like motif. J Biol Chem 2001;277:439–444.

    PubMed  Google Scholar 

  92. Okada H, Suh WK, Jin J, et al. Generation and characterization of Smac/DIABLO-deficient mice. Mol Cell Biol 2002;22:3509–3517.

    PubMed  CAS  Google Scholar 

  93. Jones JM, Datta P, Srinivasula SM, et al. Loss of OMI mitochondrial protease activity causes the neuromuscular disorder of mnd2 mutant mice. Nature 2003;425:721–727.

    PubMed  CAS  Google Scholar 

  94. Martins LM, Morrison A, Klupsch K, et al. Neuroprotective role of the reaper-related serine protease HTRA2/OMI revealed by targeted deletion in mice. Mol Cell Biol 2004;24:9848–9862.

    PubMed  CAS  Google Scholar 

  95. Clem RJ, Miller LK. Control of programmed cell death by the baculovirus genes p35 and IAP. Molecular & Cellular Biology 1994;14:5212–5222.

    CAS  Google Scholar 

  96. Hawkins CJ, Ekert PG, Uren AG, Holmgreen SP, Vaux DL. Anti-apoptotic potential of insect cellular and viral IAPs in mammalian cells. Cell Death & Differentiation 1998;5:569–576.

    CAS  Google Scholar 

  97. Seshagiri S, Miller LK. Baculovirus inhibitors of apoptosis (IAPs) block activation of sf-caspase-1. Proc Natl Acad Sci USA 1997;94:13,606–13,611.

    PubMed  CAS  Google Scholar 

  98. Harvey AJ, Soliman H, Kaiser WJ, Miller LK. Anti-and pro-apoptotic activities of baculovirus and drosophila IAPs in an insect cell line. Cell Death Differ 1997;4:733–744.

    PubMed  CAS  Google Scholar 

  99. Wright CW, Means JC, Penabaz T, Clem RJ. The baculovirus anti-apoptotic protein Op-IAP does not inhibit drosophila caspases or apoptosis in drosophila S2 cells and instead sensitizes S2 cells to virus-induced apoptosis. Virology 2005;335:61–71.

    PubMed  CAS  Google Scholar 

  100. Quinn LM, Dorstyn L, Mills K, et al. An essential role for the caspase Dronc in developmentally programmed cell death in drosophila. J Biol Chem 2000;275:40,416–40,424.

    PubMed  CAS  Google Scholar 

  101. Meier P, Silke J, Leevers SJ, Evan GI. The drosophila caspase Dronc is regulated by DIAP1. EMBO J 2000;19:598–611.

    PubMed  CAS  Google Scholar 

  102. Kaiser WJ, Vucic D, Miller LK. The drosophila inhibitor of apoptosis d-IAP1 suppresses cell death induced by the caspase Drice. FEBS Letters 1998;440:243–248.

    PubMed  CAS  Google Scholar 

  103. Harlin H, Reffey SB, Duckett CS, Lindsten T, Thompson CB. Characterization of XIAPdeficient mice. Mol Cell Biol 2001;21:3604–3608.

    PubMed  CAS  Google Scholar 

  104. Conze DB, Albert L, Ferrick DA, et al. Posttranscriptional downregulation of c-IAP2 by the ubiquitin protein ligase c-IAP1 in vivo. Mol Cell Biol 2005;25:3348–3356.

    PubMed  CAS  Google Scholar 

  105. Hao Y, Sekine K, Kawabata A, et al. Apollon ubiquitinates Smac and caspase-9, and has an essential cytoprotection function. Nat Cell Biol 2004;6:849–860.

    PubMed  CAS  Google Scholar 

  106. Vaux DL, Silke J. HTRA2/OMI, a sheep in wolf’s clothing. Cell 2003;115:251–253.

    PubMed  CAS  Google Scholar 

  107. Imoto I, Yang ZQ, Pimkhaokham A, et al. Identification of cIAP1 as a candidate target gene within an amplicon at 11q22 in esophageal squamous cell carcinomas. Cancer Res 2001;61:6629–6634.

    PubMed  CAS  Google Scholar 

  108. Nakagawa Y, Hasegawa M, Kurata M, et al. Expression of IAP-family proteins in adult acute mixed lineage leukemia (AMLL). Am J Hematol 2005;78:173–180.

    PubMed  CAS  Google Scholar 

  109. Yamamoto K, Abe S, Nakagawa Y, et al. Expression of IAP family proteins in myelodysplastic syndromes transforming to overt leukemia. Leuk Res 2004;28:1203–1211.

    PubMed  CAS  Google Scholar 

  110. Nemoto T, Kitagawa M, Hasegawa M, et al. Expression of IAP family proteins in esophageal cancer. Exp Mol Pathol 2004;76:253–259.

    PubMed  CAS  Google Scholar 

  111. Krajewska M, Krajewski S, Banares S, et al. Elevated expression of inhibitor of apoptosis proteins in prostate cancer. Clin Cancer Res 2003;9:4914–4925.

    PubMed  CAS  Google Scholar 

  112. Oost TK, Sun C, Armstrong RC, et al. Discovery of potent antagonists of the antiapoptotic protein xiap for the treatment of cancer. J Med Chem 2004;47:4417–4426.

    PubMed  CAS  Google Scholar 

  113. Li L, Thomas RM, Suzuki H, De Brabander JK, Wang X, Harran PG. A small molecule Smac mimic potentiates TRAIL-and TNFalpha-mediated cell death. Science 2004;305:1471–1474.

    PubMed  CAS  Google Scholar 

  114. Schimmer AD, Welsh K, Pinilla C, et al. Small-molecule antagonists of apoptosis suppressor XIAP exhibit broad antitumor activity. Cancer Cell 2004;5:25–35.

    PubMed  CAS  Google Scholar 

  115. Vaux DL, Silke J. IAPs, RINGs and ubiquitylation. Nat Rev Mol Cell Biol 2005;6:287–297.

    PubMed  CAS  Google Scholar 

  116. Wilson R, Goyal L, Ditzel M, et al. The DIAP1 ring finger mediates ubiquitination of Dronc and is indispensable for regulating apoptosis. Nat Cell Biol 2002;4:445–450.

    PubMed  CAS  Google Scholar 

  117. Holley CL, Olson MR, Colon-Ramos DA, Kornbluth S. Reaper eliminates IAP proteins through stimulated IAP degradation and generalized translational inhibition. Nat Cell Biol 2002;4:439–444.

    PubMed  CAS  Google Scholar 

  118. Hays R, Wickline L, Cagan R. Morgue mediates apoptosis in the drosophila melanogaster retina by promoting degradation of DIAP1. Nat Cell Biol 2002;4:425–431.

    PubMed  CAS  Google Scholar 

  119. Ryoo HD, Bergmann A, Gonen H, Ciechanover A, Steller H. Regulation of drosophila IAP1 degradation and apoptosis by reaper and UBCD1. Nat Cell Biol 2002;4:432–438.

    PubMed  CAS  Google Scholar 

  120. Palaga T, Osborne B. The 3d’s of apoptosis: Death, degradation and DIAPs. Nat Cell Biol 2002;4:E149–E151.

    PubMed  CAS  Google Scholar 

  121. Huang Hk, Joazeiro CAP, Bonfoco E, Kamada S, Leverson JD, Hunter T. The inhibitor of apoptosis, cIAP2, functions as a ubiquitin-protein ligase and promotes in vitro monoubiquitination of caspases-3 and-7. J Biol Chem 2000;275:26,661–26,664.

    PubMed  CAS  Google Scholar 

  122. Park SM, Yoon JB, Lee TH. Receptor interacting protein is ubiquitinated by cellular inhibitor of apoptosis proteins (c-IAP1 and c-IAP2) in vitro. FEBS Lett 2004;566:151–156.

    PubMed  CAS  Google Scholar 

  123. Morizane Y, Honda R, Fukami K, Yasuda H. X-linked inhibitor of apoptosis functions as ubiquitin ligase toward mature caspase-9 and cytosolic Smac/DIABLO. J Biochem 2005; 137:125–132.

    PubMed  CAS  Google Scholar 

  124. Shu HB, Takeuchi M, Goeddel DV. The tumor necrosis factor receptor 2 signal transducers TRAF2 and c-IAP1 are components of the tumor necrosis factor receptor 1 signaling complex. Proc Natl Acad Sci USA 1996;93:13,973–13,978.

    PubMed  CAS  Google Scholar 

  125. Bodmer JL, Schneider P, Tschopp J. The molecular architecture of the TNF superfamily. Trends Biochem Sci 2002;27:19–26.

    PubMed  CAS  Google Scholar 

  126. Micheau O, Tschopp J. Induction of tnf receptor i-mediated apoptosis via two sequential signaling complexes. Cell 2003;114:181–190.

    PubMed  CAS  Google Scholar 

  127. Li FZ, Ambrosini G, Chu EY, et al. Control of apoptosis and mitotic spindle checkpoint by Survivin. Nature 1998;396:580–584.

    PubMed  CAS  Google Scholar 

  128. Skoufias DA, Mollinari C, Lacroix FB, Margolis RL. Human Survivin is a kinetochoreassociated passenger protein. J Cell Biol 2000;151:1575–1582.

    PubMed  CAS  Google Scholar 

  129. Uren AG, Wong L, Pakusch M, et al. Survivin and the inner centromere protein INCENP show similar cell-cycle localization and gene knockout phenotype. Curr Biol 2000;10:1319–1328.

    PubMed  CAS  Google Scholar 

  130. Uren AG, Beilharz T, O’Connell MJ0, et al. Role for yeast inhibitor of apoptosis (IAP)-like proteins in cell division. Proc Natl Acad Sci USA 1999;96:10,170–10,175.

    PubMed  CAS  Google Scholar 

  131. Fraser AG, James C, Evan GI, Hengartner MO. Caenorhabditis elegans inhibitor of apoptosis protein (IAP) homologue BIR-1 plays a conserved role in cytokinesis. Curr Biol 1999;9:292–301.

    PubMed  CAS  Google Scholar 

  132. Jones G, Jones D, Zhou L, Steller H, Chu Y. Deterin, a new inhibitor of apoptosis from drosophila melanogaster. J Biol Chem 2000;275:22,157–22,165.

    PubMed  CAS  Google Scholar 

  133. Oeda E, Oka Y, Miyazono K, Kawabata M. Interaction of drosophila inhibitors of apoptosis with thick veins, a type I serine/threonine kinase receptor for decapentaplegic. J Biol Chem 1998;273:9353–9356.

    PubMed  CAS  Google Scholar 

  134. Yamaguchi K, Nagai S, Ninomiya-Tsuji J, et al. XIAP, a cellular member of the inhibitor of apoptosis protein family, links the receptors to TAB1-TAK1 in the BMP signaling pathway. EMBO J 1999;18:179–187.

    PubMed  CAS  Google Scholar 

  135. Birkey Reffey S, Wurthner JU, Parks WT, Roberts AB, Duckett CS. X-linked inhibitor of apoptosis protein functions as a cofactor in transforming growth factor-beta signaling. J Biol Chem 2001;276:26,542–26,549.

    PubMed  CAS  Google Scholar 

  136. Massague J, Chen YG. Controlling TGF-beta signaling. Genes Dev 2000;14:627–644.

    PubMed  CAS  Google Scholar 

  137. Sanna MG, Duckett CS, Richter B, Thompson CB, Ulevitch RJ. Selective activation of JNK1 is necessary for the anti-apoptotic activity of HILP. Proc Natl Acad Sci USA 1998;95:6015–6020.

    PubMed  CAS  Google Scholar 

  138. Sanna MG, da Silva Correia J, Luo Y, et al. ILPIP, a novel anti-apoptotic protein that enhances XIAP-mediated activation of JNK1 and protection against apoptosis. J Biol Chem 2002;277:30,454–30,462.

    PubMed  CAS  Google Scholar 

  139. Silke J, Kratina T, Chu D, et al. Determination of cell survival by RING-mediated regulation of IAP abundance. Proc Natl Acad Sci USA 2005;102:16,182–16,187.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia

    Jai Y. Yu, John Silke & Paul G. Ekert

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  1. Jai Y. Yu
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  2. John Silke
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  3. Paul G. Ekert
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  1. Department of Biochemistry, University of Texas Health Center at Tyler, Tyler, TX

    Rakesh Srivastava

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Yu, J.Y., Silke, J., Ekert, P.G. (2006). Inhibitor of Apoptosis Proteins and Caspases. In: Srivastava, R. (eds) Apoptosis, Cell Signaling, and Human Diseases. Humana Press. https://doi.org/10.1007/978-1-59745-199-4_15

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